The major objective is to elucidate the role of early nutritional experiences on the developmental aspects of dietary calorigenesis and related areas of carbohydrate and lipid metabolism during early phases in the development of obesity. Two varieties of genetically obese rodents will be used; the obese hyperglycemic mouse (ob/ob) and the Zucker fatty rat (fa/fa). The project also proposes to study the observed defective regulation of oxidative metabolism which precedes most other abnormalities associated with early onset obesity. Energy expenditure in tissues will be evaluated at the cellular and mitochondrial levels during the early phases of obese development, when obesity cannot be easily recognized by elevated body weight or appearance. We will ascertain which tissues reflect the lower oxygen consumption exhibited by liver obese rodents. The effects of dietary fat and carbohydrate and physical activity, introduced at weaning, on the development of energy expenditure (calorigenesis) at the gross, cellular and mitochondrial levels will be evaluated. As development proceeds, oxygen consumption of the whole animal, tissues, and mitochondrial preparations will be determined. The activities of selected mitochondrial enzymes will also be determined. The influence of dietary fat and carbohydrate as well as physical activity on these parameters of energy metabolism and body composition will be studied. The development of insulin resistance by tissues of obese rodents may be related to impaired energy metabolism in these tissues. The action of insulin and thyroid hormones on glucose transport, oxidation, and utilization will be studied during the early and later phases in the development of obesity. The results of the proposed investigations should increase our understanding of the role that early dietary experiences may have on the development of energy metabolism, body composition, and adiposity.